Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group

Lauren M. Postlewait, Cecilia G. Ethun, Thuy B. Tran, Jason D. Prescott, Timothy M. Pawlik, Tracy S. Wang, Jason Glenn, Ioannis Hatzaras, Rivfka Shenoy, John E. Phay, Kara Keplinger, Ryan C. Fields, Linda X. Jin, Sharon M. Weber, Ahmed Salem, Jason K. Sicklick, Shady Gad, Adam C. Yopp, John C. Mansour, Quan Yang DuhNatalie Seiser, Carmen C. Solorzano, Colleen M. Kiernan, Konstantinos I. Votanopoulos, Edward A. Levine, Charles A. Staley, George A. Poultsides, Shishir K. Maithel

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Abstract

Background Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Study Design Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Results Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p <0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. Conclusions When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

Original languageEnglish (US)
Pages (from-to)480-490
Number of pages11
JournalJournal of the American College of Surgeons
Volume222
Issue number4
DOIs
StatePublished - Apr 1 2016

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Mitotane
Adrenocortical Carcinoma
Survival
Recurrence
Adjuvant Chemotherapy
Rupture
Guidelines
Neoplasms
Mitotic Index
Survival Analysis
Practice Guidelines

ASJC Scopus subject areas

  • Surgery

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Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma : A 13-Institution Study by the US Adrenocortical Carcinoma Group. / Postlewait, Lauren M.; Ethun, Cecilia G.; Tran, Thuy B.; Prescott, Jason D.; Pawlik, Timothy M.; Wang, Tracy S.; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Staley, Charles A.; Poultsides, George A.; Maithel, Shishir K.

In: Journal of the American College of Surgeons, Vol. 222, No. 4, 01.04.2016, p. 480-490.

Research output: Contribution to journalArticle

Postlewait, LM, Ethun, CG, Tran, TB, Prescott, JD, Pawlik, TM, Wang, TS, Glenn, J, Hatzaras, I, Shenoy, R, Phay, JE, Keplinger, K, Fields, RC, Jin, LX, Weber, SM, Salem, A, Sicklick, JK, Gad, S, Yopp, AC, Mansour, JC, Duh, QY, Seiser, N, Solorzano, CC, Kiernan, CM, Votanopoulos, KI, Levine, EA, Staley, CA, Poultsides, GA & Maithel, SK 2016, 'Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group', Journal of the American College of Surgeons, vol. 222, no. 4, pp. 480-490. https://doi.org/10.1016/j.jamcollsurg.2015.12.013
Postlewait, Lauren M. ; Ethun, Cecilia G. ; Tran, Thuy B. ; Prescott, Jason D. ; Pawlik, Timothy M. ; Wang, Tracy S. ; Glenn, Jason ; Hatzaras, Ioannis ; Shenoy, Rivfka ; Phay, John E. ; Keplinger, Kara ; Fields, Ryan C. ; Jin, Linda X. ; Weber, Sharon M. ; Salem, Ahmed ; Sicklick, Jason K. ; Gad, Shady ; Yopp, Adam C. ; Mansour, John C. ; Duh, Quan Yang ; Seiser, Natalie ; Solorzano, Carmen C. ; Kiernan, Colleen M. ; Votanopoulos, Konstantinos I. ; Levine, Edward A. ; Staley, Charles A. ; Poultsides, George A. ; Maithel, Shishir K. / Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma : A 13-Institution Study by the US Adrenocortical Carcinoma Group. In: Journal of the American College of Surgeons. 2016 ; Vol. 222, No. 4. pp. 480-490.
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title = "Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A 13-Institution Study by the US Adrenocortical Carcinoma Group",
abstract = "Background Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Study Design Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Results Of 207 patients, 88 (43{\%}) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58{\%} vs 32{\%}; p = 0.001), advanced TNM stage (stage IV: 42{\%} vs 23{\%}; p = 0.021), adjuvant chemotherapy (37{\%} vs 5{\%}; p <0.001), and adjuvant radiation (17{\%} vs 5{\%}; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. Conclusions When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.",
author = "Postlewait, {Lauren M.} and Ethun, {Cecilia G.} and Tran, {Thuy B.} and Prescott, {Jason D.} and Pawlik, {Timothy M.} and Wang, {Tracy S.} and Jason Glenn and Ioannis Hatzaras and Rivfka Shenoy and Phay, {John E.} and Kara Keplinger and Fields, {Ryan C.} and Jin, {Linda X.} and Weber, {Sharon M.} and Ahmed Salem and Sicklick, {Jason K.} and Shady Gad and Yopp, {Adam C.} and Mansour, {John C.} and Duh, {Quan Yang} and Natalie Seiser and Solorzano, {Carmen C.} and Kiernan, {Colleen M.} and Votanopoulos, {Konstantinos I.} and Levine, {Edward A.} and Staley, {Charles A.} and Poultsides, {George A.} and Maithel, {Shishir K.}",
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TY - JOUR

T1 - Outcomes of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma

T2 - A 13-Institution Study by the US Adrenocortical Carcinoma Group

AU - Postlewait, Lauren M.

AU - Ethun, Cecilia G.

AU - Tran, Thuy B.

AU - Prescott, Jason D.

AU - Pawlik, Timothy M.

AU - Wang, Tracy S.

AU - Glenn, Jason

AU - Hatzaras, Ioannis

AU - Shenoy, Rivfka

AU - Phay, John E.

AU - Keplinger, Kara

AU - Fields, Ryan C.

AU - Jin, Linda X.

AU - Weber, Sharon M.

AU - Salem, Ahmed

AU - Sicklick, Jason K.

AU - Gad, Shady

AU - Yopp, Adam C.

AU - Mansour, John C.

AU - Duh, Quan Yang

AU - Seiser, Natalie

AU - Solorzano, Carmen C.

AU - Kiernan, Colleen M.

AU - Votanopoulos, Konstantinos I.

AU - Levine, Edward A.

AU - Staley, Charles A.

AU - Poultsides, George A.

AU - Maithel, Shishir K.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Study Design Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Results Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p <0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. Conclusions When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

AB - Background Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Study Design Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Results Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p <0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. Conclusions When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.

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